Fludarabine Phosphate (Page 5 of 5)

14 CLINICAL STUDIES

14.1 Adults

Two single-arm open-label studies of fludarabine phosphate have been conducted in adult patients with CLL refractory to at least one prior standard alkylating-agent containing regimen. In a study conducted by M.D. Anderson Cancer Center (MDAH), 48 patients were treated with a dose of 22 to 40 mg/m ² daily for 5 days every 28 days. Another study conducted by the Southwest Oncology Group (SWOG) involved 31 patients treated with a dose of 15 to 25 mg/m ² daily for 5 days every 28 days. The overall objective response rates were 48% and 32% in the MDAH and SWOG studies, respectively. The complete response rate in both studies was 13%; the partial response rate was 35% in the MDAH study and 19% in the SWOG study. These response rates were obtained using standardized response criteria developed by the National Cancer Institute CLL Working Group and were achieved in heavily pretreated patients. The ability of fludarabine phosphate to induce a significant rate of response in refractory patients suggests minimal cross-resistance with commonly used anti-CLL agents.

The median time to response in the MDAH and SWOG studies was 7 weeks (range of 1 to 68 weeks) and 21 weeks (range of 1 to 53 weeks), respectively. The median duration of disease control was 91 weeks (MDAH) and 65 weeks (SWOG). The median survival of all refractory CLL patients treated with fludarabine phosphate was 43 weeks and 52 weeks in the MDAH and SWOG studies, respectively.

Rai stage improved to Stage II or better in 7 of 12 MDAH responders (58%) and in 5 of 7 SWOG responders (71%) who were Stage III or IV at baseline. In the combined studies, mean hemoglobin concentration improved from 9.0 g/dL at baseline to 11.8 g/dL at the time of response in a subgroup of anemic patients. Similarly, average platelet count improved from 63,500/mm ³ to 103,300/mm ³ at the time of response in a subgroup of patients who were thrombocytopenic at baseline.

15 REFERENCES

1. Preventing Occupational Exposures to Antineoplastic and Other Hazardous Drugs in Health Care Settings. NIOSH Alert 2004-165.
2. OSHA Technical Manual, TED 1-0.l5A, Section VI: Chapter 2. Controlling Occupational Exposure to Hazardous Drugs. OSHA, 1999. http://www.osha.gov/dts/osta/otm/otm_vi/otim_vi_2.html
3. American Society of Health-System Pharmacists. ASHP guidelines on handling hazardous drugs.

Am J Health-Syst Pharm. 2006; 63:172-1193.

1. Polovich, M., White, J. M., & Kelleher, L.O. (eds.) 2005. Chemotherapy and biotherapy guidelines and recommendations for practice (2nd. ed.) Pittsburgh, PA: Oncology Nursing Society

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

Fludarabine Phosphate Injection, USP is supplied as a sterile solution containing 50 mg/2 mL (25 mg/mL) of fludarabine phosphate in a 2 mL single use vial.

NDC 59923-604-02 one carton containing 1 vial of Fludarabine Phosphate Injection.

16.2 Storage

Store refrigerated between 2° and 8°C (36° and 46°F).

16.3 Handling and Disposal

Procedures for proper handling and disposal should be considered. Consideration should be given to handling and disposal according to guidelines issued for cytotoxic drugs. Several guidelines on this subject have been published. ^1-4 Caution should be exercised in the handling and preparation of Fludarabine Phosphate Injection solution. The use of latex gloves and safety glasses is recommended to avoid exposure in case of breakage of the vial or other accidental spillage. If the solution contacts the skin or mucous membranes, wash thoroughly with soap and water; rinse eyes thoroughly with plain water. Avoid exposure by inhalation or by direct contact of the skin or mucous membranes.

17 PATIENT COUNSELING INFORMATION

17.1 Monitoring

Patients should be informed of the importance of periodic assessment of their blood count to detect the development of anemia, neutropenia and thrombocytopenia.

17.2 Laboratory Tests

During treatment, the patient’s hematologic profile (particularly neutrophils, red blood cells, and platelets) should be monitored regularly to determine the degree of hematopoietic suppression [see Warnings and Precautions (5.2)].

17.3 Pregnancy

Fludarabine phosphate can cause fetal harm when administered to a pregnant woman. Women should be advised to avoid becoming pregnant [see Warnings and Precautions (5.6)].

Manufactured for:

Areva Pharmaceuticals Inc.

Georgetown, IN 47122

Made in Italy

Revised: October 2018

PACKAGE LABEL PRINCIPAL DISPLAY PANEL

Vial Label

Carton Label

FLUDARABINE PHOSPHATE fludarabine phosphate injection

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:59923-604 Route of Administration INTRAVENOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength FLUDARABINE PHOSPHATE (FLUDARABINE) FLUDARABINE PHOSPHATE 25 mg in 1 mL

Inactive Ingredients Ingredient Name Strength SODIUM HYDROXIDE MANNITOL WATER

Packaging # Item Code Package Description Multilevel Packaging 1 NDC:59923-604-02 1 VIAL, SINGLE-DOSE in 1 CARTON contains a VIAL, SINGLE-DOSE 1 2 mL in 1 VIAL, SINGLE-DOSE This package is contained within the CARTON (59923-604-02)

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA090724 12/31/2019

Labeler — Areva Pharmaceuticals (833189835)

Registrant — Areva Pharmaceuticals (833189835)

Establishment
Name	Address	ID/FEI	Operations
NerPharMa SRL		338839192	manufacture (59923-604)

Revised: 01/2021 Areva Pharmaceuticals